BACKGROUND: Identifying infants with congenital infection for early intervention will likely be challenging in future Zika virus outbreaks. We investigated indicators of risk for developmental delay among children born with and without obvious manifestations of congenital Zika virus infection. METHODS: We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraíba, Brazil. We analyzed data from children at birth; ages 1-7 months and approximately 24 months, using medical records (i.e., anthropometric measurements diagnoses), medical evaluation (i.e., Zika/other laboratory tests, dysmorphic features), and parent report (seizures, developmental delay). We used a Bayesian modeling approach to identify predictors of developmental delay. RESULTS: Head circumference (HC) and length at birth and rates of growth for HC and length at follow-up were consistent across domains of developmental delay; (e.g., for every 1 cm per month decrease in HC growth rate; there was a corresponding decrease in the gross motor z-score). Modeling results indicated that HC and length at birth, and follow-up HC and length rates of growth, were predictive of developmental delay. CONCLUSION: These findings suggest that accurate measurement and frequent monitoring of HC and length, especially in the first few months of life, may be useful for identifying children possibly congenitally exposed to Zika virus who could benefit from early intervention services.

On June 1, 2020, with declines in coronavirus disease 2019 (COVID-19) cases and hospitalizations in Rhode Island,* child care programs in the state reopened after a nearly 3-month closure implemented as part of mitigation efforts. To reopen safely, the Rhode Island Department of Human Services (RIDHS) required licensed center- and home-based child care programs to reduce enrollment, initially to a maximum of 12 persons, including staff members, in stable groups (i.e., staff members and students not switching between groups) in physically separated spaces, increasing to a maximum of 20 persons on June 29. Additional requirements included universal use of masks for adults, daily symptom screening of adults and children, and enhanced cleaning and disinfection according to CDC guidelines.(†) As of July 31, 666 of 891 (75%) programs were approved to reopen, with capacity for 18,945 children, representing 74% of the state's January 2020 child care program population (25,749 children).

The etiologic agent of the outbreak of pneumonia in Wuhan China was identified as severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) in January, 2020. The first US patient was diagnosed by the State of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens, and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into two virus repositories, making it broadly available to the public health and research communities. We hope that open access to this important reagent will expedite development of medical countermeasures.

The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.

This article describes novel methods of applying the Ages and Stages Questionnaire-3rd edition (ASQ-3) to assess and quantify developmental delay among children following the 2015-2016 Zika virus outbreak in Brazil. Many of the children with Zika virus infection were expected to have severe developmental delay. However, administering the ASQ-3 to caregivers of these children according to standard protocol would have screened for the overall presence of delay but not the severity of delay. We adopted an amended protocol for administration of the ASQ-3 to quantify the developmental functioning of children severely affected by Zika virus infection in this investigation. Protocols for administering the ASQ-3 among this population were drafted in consultation with developmental measurement experts and are presented here. Specific developmental estimates are discussed, including developmental age equivalents, developmental quotients, and developmental quotient z scores. The calculations of these estimates are presented with examples in the context of the 2015-2016 Zika virus outbreak and associated microcephaly among prenatally infected children from 2 states in northeastern Brazil. Potential applications of these methods for estimating developmental ability among similar pediatric populations are discussed.

Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraiba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.

Introduction: Hardened smokers are those who do not want to quit, or find it very difficult to quit. This study assessed the prevalence and predictors of hardened smokers in 19 low- and middle-income countries (LMICs). | | Methods: We used nationally representative data from 19 LMICs that conducted the Global Adult Tobacco Survey during 2009-2013. Our analysis is restricted to adults aged ≥25 years. Hardened smokers were defined as daily smokers who smoked for 5 or more years, and who reported the following: no quit attempt in the past year that lasted 24 or more hours; no interest in quitting, or not planning to quit in the next year; and currently smoked within 30 minutes after waking. For each country, the prevalence of hardened smokers was analyzed by sex, age, residence (urban or rural), educational attainment, wealth index, and knowledge of the danger of smoking. Multivariable logistic regression was used to assess predictors of hardened smoking. | | Results: Prevalence of hardened smokers among adults (aged ≥25 years) ranged from 1.1% (Panama) to 14.3% (Russia). Among current smokers (aged ≥25 years), the proportion of hardened smokers ranged from 7.5% (Mexico) to 38.4% (Romania). Adjusted odds of hardened smokers were significantly higher for males (9 of 19 countries), smokers aged 65 years or older (12 of 19 countries), adults with lower educational attainment (9 of 19 countries), and no knowledge of the danger of smoking (8 of 19 countries). | | Conclusions: The spectrum of smokers in the LMICs includes hardened smokers and prevalence varies across population groups. Full implementation of proven tobacco control strategies could reduce hardened smoking in LMICs.

Currently, no federal policies exist in the United States regarding private wells; this authority is devolved to states. This study inventoried state-level policies governing private wells in the United States in order to identify the topics addressed by each state, division of responsibilities across state agencies, and geographic differences in policy comprehensiveness. From May to August 2018, two independent reviewers conducted an online search followed by directly contacting state agencies (98% response) to identify all state-level policies in the United States that directly reference private wells. The search, updated in April 2018, confirmed the existing water policy list and identified 23 additional policies. Policies were then coded according to nine not-mutually-exclusive classifications. The results indicate that all states had at least one policy addressing private well drilling or construction. Significant geographic differences exist in maintenance related policies. In conclusion, although drilling and construction safety are addressed by each state, some policy domains are addressed inconsistently across states, and other policy domains are absent in most states. © IWA Publishing 2019.

On January 13, 2018, at 8:07 a.m. Hawaii Standard Time, an errant emergency alert was sent to persons in Hawaii. An employee at the Hawaii Emergency Management Agency (EMA) sent the errant alert via the Wireless Emergency Alert (WEA) system and the Emergency Alert System (EAS) during a ballistic missile preparedness drill, advising persons to seek shelter from an incoming ballistic missile. WEA delivers location-based warnings to wireless carrier systems, and EAS sends alerts via television and radio (1). After 38 minutes, at 8:45 a.m., Hawaii EMA retracted the alert via WEA and EAS (2). To understand the impact of the alert, social media responses to the errant message were analyzed. Data were extracted from Twitter* using a Boolean search for tweets (Twitter postings) posted on January 13 regarding the false alert. Tweets were analyzed during two 38-minute periods: 1) early (8:07-8:45 a.m.), the elapsed time the errant alert circulated until the correction was issued and 2) late (8:46-9:24 a.m.), the same amount of elapsed time after issuance of the correction. A total of 5,880 tweets during the early period and 8,650 tweets during the late period met the search criteria. Four themes emerged during the early period: information processing, information sharing, authentication, and emotional reaction. During the late period, information sharing and emotional reaction themes persisted; denunciation, insufficient knowledge to act, and mistrust of authority also emerged as themes. Understanding public interpretation, sharing, and reaction to social media messages related to emergencies can inform development and dissemination of accurate public health messages to save lives during a crisis.

Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

Antimalarial drug resistance is a major constraint for malaria control and elimination efforts. Artemisinin-based combination therapy is now the mainstay for malaria treatment. However, delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong Sub region and may emerge or spread to other malaria endemic regions. This spread is of great concern for malaria control programmes, as no alternatives to artemisinin-based combination therapies are expected to be available in the near future. There is a need to strengthen surveillance systems for early detection and response to the antimalarial drug resistance threat. Current surveillance is mainly done through therapeutic efficacy studies; however these studies are complex and both time- and resource-intensive. For multiple common antimalarials, parasite drug resistance has been correlated with specific genetic mutations, and the molecular markers associated with antimalarial drug resistance offer a simple and powerful tool to monitor the emergence and spread of resistant parasites. Different techniques to analyse molecular markers associated with antimalarial drug resistance are available, each with advantages and disadvantages. However, procedures are not adequately harmonized to facilitate comparisons between sites. Here we describe the target product profiles for tests to analyse molecular markers associated with antimalarial drug resistance, discuss how use of current techniques can be standardised, and identify the requirements for an ideal product that would allow malaria endemic countries to provide useful spatial and temporal information on the spread of resistance.

Commercial malaria rapid diagnostic tests (RDTs) detect P. falciparum histidine rich protein 2 (PfHRP2) and cross react with PfHRP3, a structural homologue. Here, we analysed natural variations in PfHRP2 and PfHRP3 sequences from Indian isolates and correlated these variations with RDT reactivity. A total 1392 P. falciparum positive samples collected from eight endemic states were PCR amplified for Pfhrp2 and Pfhrp3 genes and were sequenced. The deduced protein sequences were analysed for repeat variations and correlated with RDT reactivity. Out of 1392 PCR amplified samples, a single sample was Pfhrp2 negative and two samples were Pfhrp3 negative. Complete Pfhrp2 and Pfhrp3 sequences were obtained for 769 samples and 750 samples, respectively. A total of 16 distinct repeat motifs were observed for Pfhrp2 and 11 for Pfhrp3, including some new repeat types. No correlation was found between variations in the size of Pfhrp2 repeat types 2 and 7, nor between any combinations of repeat motifs, and performance of a commercial RDT at low parasite densities. The findings suggest that sequence diversity in Pfhrp2 and Pfhrp3 genes in Indian isolates is not likely to negatively influence performance of currently used PfHRP2 RDTs.

The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016. In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures, strategies to protect pregnant women, syndromic surveillance based on electronic health record (EHR) reports, Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance. All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January-February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance indicated a return to pre-outbreak levels. The last Zika virus disease case detected by real-time, reverse transcription-polymerase chain reaction (rRT-PCR) occurred in a patient who had symptom onset on June 19, 2016. In August 2016, ASDoH requested CDC support in assessing whether local transmission had been reduced or interrupted and in proposing a timeline for discontinuation of routine testing of asymptomatic pregnant women. An end date (October 15, 2016) was determined for active mosquito-borne transmission of Zika virus and a timeline was developed for discontinuation of routine screening of asymptomatic pregnant women in American Samoa (conception after December 10, 2016, with permissive testing for asymptomatic women who conceive through April 15, 2017).

The unique characteristics of children dictate the need for school-based all-hazards response plans during natural disasters, emerging infectious diseases, and terrorism. Schools are a critical community institution serving a vulnerable population that must be accounted for in public health preparedness plans; prepared schools are adopting policies and plans for crisis preparedness, response, and recovery. The importance of having such plans in place is underscored by the development of a new Healthy People 2020 objective (PREP-5) to "increase the percentage of school districts that require schools to include specific topics in their crisis preparedness, response, and recovery plans". Because decisions about such plans are usually made at the school district level, it is important to examine district-level policies and practices. Although previous reports have provided national estimates of the percentage of districts with policies and practices in place, these estimates have not been analyzed by U.S. Census region* and urbanicity.dagger Using data from the 2012 School Health Policies and Practices Study (SHPPS), this report examines policies and practices related to school district preparedness, response, and recovery. In general, districts in the Midwest were less likely to require schools to include specific topics in their crisis preparedness plans than districts in the Northeast and South. Urban districts tended to be more likely than nonurban districts to require specific topics in school preparedness plans. Southern districts tended to be more likely than districts in other regions to engage with partners when developing plans. No differences in district collaboration (with the exception of local fire department engagement) were observed by level of urbanicity. School-based preparedness planning needs to be coordinated with interdisciplinary community partners to achieve Healthy People 2020 PREP-5 objectives for this vulnerable population.

BACKGROUND: Plasmodium falciparum encoded histidine rich protein (HRP2) based malaria rapid diagnostic tests (RDTs) are used in India. Deletion of pfhrp2 and pfhrp3 genes contributes to false negative test results, and large numbers of such deletions have been reported from South America, highlighting the importance of surveillance to detect such deletions. METHODS: This is the first prospective field study carried out at 16 sites located in eight endemic states of India to assess the performance of PfHRP2 based RDT kits used in the national malaria control programme. In this study, microscopically confirmed P. falciparum but RDT negative samples were assessed for presence of pfhrp2, pfhrp3, and their flanking genes using PCR. RESULTS: Among 1521 microscopically positive P. falciparum samples screened, 50 were negative by HRP2 based RDT test. Molecular testing was carried out using these 50 RDT negative samples by assuming that 1471 RDT positive samples carried pfhrp2 gene. It was found that 2.4% (36/1521) and 1.8% (27/1521) of samples were negative for pfhrp2 and pfhrp3 genes, respectively. However, the frequency of pfhrp2 deletions varied between the sites ranging from 0-25% (2.4, 95% CI; 1.6-3.3). The frequency of both pfhrp2 and pfhrp3 gene deletion varied from 0-8% (1.6, 95% CI; 1.0-2.4). CONCLUSION: This study provides evidence for low level presence of pfhrp2 and pfhrp3 deleted P. falciparum parasites in different endemic regions of India, and periodic surveillance is warranted for reliable use of PfHRP2 based RDTs.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degreeC) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

OBJECTIVES: Natural and man-made disasters can result in power outages that can affect certain vulnerable populations dependent on electrically powered durable medical equipment. This study estimated the size and prevalence of that electricity-dependent population residing at home in the United States. METHODS: We used the Truven Health MarketScan 2012 database to estimate the number of employer-sponsored privately insured enrollees by geography, age group, and sex who resided at home and were dependent upon electrically powered durable medical equipment to sustain life. We estimated nationally representative prevalence and used US Census population estimates to extrapolate the national population and produce maps visualizing prevalence and distribution of electricity-dependent populations residing at home. RESULTS: As of 2012, among the 175 million persons covered by employer-sponsored private insurance, the estimated number of electricity-dependent persons residing at home was 366 619 (95% confidence interval: 365 700-367 537), with a national prevalence of 218.2 per 100 000 covered lives (95% confidence interval: 217.7-218.8). Prevalence varied significantly by age group (chi = 264 289 95, P < .0001) and region (chi = 12 286 30, P < .0001), with highest prevalence in those 65 years of age or older and in the South and the West. Across all insurance types in the United States, approximately 685 000 electricity-dependent persons resided at home. CONCLUSIONS: These results may assist public health jurisdictions addressing unique needs and necessary resources for this particularly vulnerable population. Results can verify and enhance the development of functional needs registries, which are needed to help first responders target efforts to those most vulnerable during disasters affecting the power supply.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 35% of vaccinees. Vaccine viremia was detected within 3 days in 103 of 110 participants (94%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days; 2 self-limited cases occurred in 40 participants (5%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099 , NCT02287480 , and NCT02296983 ; Pan African Clinical Trials Registry number, PACTR201411000919191 .).

Pattern Recognition Receptors (PRR) sense certain molecular patterns uniquely expressed by pathogens. Retinoic-acid-inducible gene I (RIG-I) is a cytosolic PRR that senses viral nucleic acids and induces innate immune activation and secretion of type-I IFNs. Here, using influenza vaccine antigens, we investigated the consequences of activating the RIG-I pathway on antigen-specific adaptive immune responses. We found that mice immunized with influenza vaccine antigens co-administered with 5' ppp-dsRNA, a RIG-I ligand, developed robust levels of hemagglutination inhibiting antibodies, enhanced germinal center reaction and T follicular helper cell responses. In addition, RIG-I activation enhanced antibody affinity maturation and plasma cell responses in draining lymph nodes, spleen, and bone marrow and conferred protective immunity against virus challenge. Importantly, activation of RIG-I pathway was able to reduce the antigen requirement by 10-100 folds in inducing optimal influenza-specific cellular and humoral responses including protective immunity. The effects induced by 5' ppp-dsRNA were significantly dependent on type-I IFN and IPS-1 (adapter protein downstream of RIG-I pathway) signaling, but were independent of MyD88 or TLR3 mediated pathways. Our results show that activation of RIG-I-like receptor pathway programs the innate immunity to achieve qualitatively and quantitatively enhanced protective cellular adaptive immune responses even at low antigen doses and thus, indicate the potential utility of RIG-I ligands as molecular adjuvants for the viral vaccines. STUDY IMPORTANCE STATEMENT: The recently discovered RNA helicase family of RIG-I-like receptors (RLRs) is a critical component of host defense mechanisms responsible for detecting viruses and triggering innate anti-viral cytokines that help control viral replication and dissemination. In this study we show that the RLR-pathway can be effectively exploited for enhancing adaptive immunity and protective immune memory against viral infection. Our results show that activation of RIG-I pathway along with influenza vaccination programs the innate immunity to induce qualitatively and quantitatively superior protective adaptive immunity against pandemic influenza viruses. More importantly, the RIG-I activation at the time of vaccination allows induction of robust adaptive responses even at sparing vaccine antigen doses. These results highlight the potential utility of exploiting RIG-I pathway for enhancing viral vaccine specific immunity and have broader implications for designing better vaccines in general.

PROBLEM/CONDITION: At the end of 2009, an estimated 1,148,200 persons aged ≥13 years were living with human immunodeficiency virus (HIV) infection in the United States. Despite the recent decreases in HIV infection attributed to injection drug use, 8% of new HIV infections in 2010 occurred among injecting drug users (IDUs). REPORTING PERIOD: June-December 2009. DESCRIPTION OF SYSTEM: The National HIV Behavioral Surveillance System (NHBS) collects HIV prevalence and risk behavior data in selected metropolitan statistical areas (MSAs) from three populations at high risk for HIV infection: men who have sex with men, IDUs, and heterosexual adults at increased risk for HIV infection. Data for NHBS are collected in rotating cycles. For the 2009 NHBS cycle, IDUs were recruited in 20 participating MSAs using respondent-driven sampling, a peer-referral sampling method. Participants were eligible if they were aged ≥18 years, lived in a participating MSA, were able to complete a behavioral survey in English or Spanish, and reported that they had injected drugs during the past 12 months. Consenting participants completed an interviewer-administered (face-to-face), anonymous standardized questionnaire about HIV-associated behaviors, and all participants were offered anonymous HIV testing. Analysis of 2009 NHBS data represents the first large assessment of HIV prevalence among IDUs in the United States in >10 years. RESULTS: This report summarizes two separate analyses using unweighted data from 10,200 eligible IDUs in 20 MSAs from the second collection cycle of NHBS in 2009. Both an HIV infection analysis and a behavioral analysis were conducted. Different denominators were used in each analysis because of the order and type of exclusion criteria applied. For the HIV infection analysis, of the 10,200 eligible participants, 10,090 had a valid HIV test result, of whom 906 (9%) tested positive for HIV (range: 2%-19% by MSA). When 509 participants who reported receiving a previous positive HIV test result were excluded from this analysis, 4% (397 of 9,581 participants) tested HIV-positive. For the behavioral analysis, because knowledge of HIV status might influence risk behaviors, 548 participants who reported a previous HIV-positive test result were excluded from the 10,200 eligible participants. All subsequent analyses were conducted for the remaining 9,652 participants. The most commonly injected drugs during the past 12 months among these participants were heroin (90%), speedball (heroin and cocaine combined) (58%), and cocaine or crack (49%). Large percentages of participants reported receptive sharing of syringes (35%); receptive sharing of other injection equipment, such as cookers, cotton, or water (58%); and receptive sharing of syringes to divide drugs (35%). Many participants reported having unprotected sex with opposite-sex partners during the past 12 months: 70% of men and 73% of women had unprotected vaginal sex, and 25% of men and 21% of women had unprotected anal sex. A combination of unsafe injection- and sex-related behaviors during the past 12 months was commonly reported; 41% of participants who reported unprotected vaginal sex with one or more opposite-sex partners, and 53% of participants who reported unprotected anal sex with one or more opposite-sex partners also reported receptive sharing of syringes. More women than men reported having sex in exchange for money or drugs (31% and 18%, respectively). Among men, 10% had oral or anal sex with one or more male partners during the past 12 months. Many participants (74%) reported noninjection drug use during the past 12 months, and 41% reported binge drinking during the past 30 days. A large percentage of participants (74%) had ever been tested for hepatitis C, 41% had received a hepatitis C virus infection diagnosis, and 29% had received a vaccination against hepatitis A virus, hepatitis B virus, or both. Most (88%) had been tested for HIV during their lifetime, and 49% had been tested during the past 12 months. Approximately half of participants received free HIV prevention materials during the past 12 months, including condoms (50%) and sterile syringes (44%) and other injection equipment (41%). One third of participants had been in an alcohol or a drug treatment program, and 21% had participated in an individual- or a group-level HIV behavioral intervention. INTERPRETATION: IDUs in the United States continue to engage in sexual and drug-use behaviors that increase their risk for HIV infection. The large percentage of participants in this study who reported engaging in both unprotected sex and receptive sharing of syringes supports the need for HIV prevention programs to address both injection and sex-related risk behaviors among IDUs. Although most participants had been tested for HIV infection previously, less than half had been tested in the past year as recommended by CDC. In addition, many participants had not been vaccinated against hepatitis A and B as recommended by CDC. Although all participants had injected drugs during the past year, only a small percentage had recently participated in an alcohol or a drug treatment program or in a behavioral intervention, suggesting an unmet need for drug treatment and HIV prevention services. PUBLIC HEALTH ACTION: To reduce the number of HIV infections among IDUs, additional efforts are needed to decrease the number of persons who engage in behaviors that increase their risk for HIV infection and to increase their access to HIV testing, alcohol and drug treatment, and other HIV prevention programs. The National HIV/AIDS Strategy for the United States delineates a coordinated response to reduce HIV incidence and HIV-related health disparities among IDUs and other disproportionately affected groups. CDC's high-impact HIV prevention approach provides an essential step toward achieving these goals by using combinations of scientifically proven, cost-effective, and scalable interventions among populations at greatest risk. NHBS data can be used to monitor progress toward the national strategy goals and to guide national and local planning efforts to maximize the impact of HIV prevention programs.

We studied 2941 young gay, bisexual, and other men who have sex with men using National HIV Behavioral Surveillance System data. Within the past 12 months, 88.9% used health care, suggesting many opportunities for recommended care including human papillomavirus vaccination. However, only 61.3% disclosed male-male sexual attraction/behavior to a provider, which may result in some opportunities being missed.

Respondent-driven sampling (RDS) has become increasingly popular for sampling hidden populations, including injecting drug users (IDU). However, RDS data are unique and require specialized analysis techniques, many of which remain underdeveloped. RDS sample size estimation requires knowing design effect (DE), which can only be calculated post hoc. Few studies have analyzed RDS DE using real world empirical data. We analyze estimated DE from 43 samples of IDU collected using a standardized protocol. We find the previous recommendation that sample size be at least doubled, consistent with DE=2, underestimates true DE and recommend researchers use DE=4 as an alternate estimate when calculating sample size. A formula for calculating sample size for RDS studies among IDU is presented. Researchers faced with limited resources may wish to accept slightly higher standard errors to keep sample size requirements low. Our results highlight dangers of ignoring sampling design in analysis.

OBJECTIVES: We conducted a case study of an urban immunization outreach strategy to determine the feasibility of the intervention and to measure administrative immunization coverage outcomes. METHODS: A multipronged strategy for improving immunization coverage in Urban Patna, India, was implemented for 1 year (2009/2010). The strategy was designed to increase immunization sites, shift human resources, plan logistics, improve community mobilization, provide supervision, strengthen data flow and implement special vaccination drives. RESULTS: Over 1 year, the coverage of all primary vaccines of the Universal Immunization Program improved by over 100%. CONCLUSION: Coverage can be rapidly improved through outreach immunization in low socioeconomic areas if existing opportunities are carefully utilized.

Trypanosoma cruzi is a protozoan parasite that causes human Chagas' disease, a leading source of congestive heart failure in Central and South America. CD8+ T cells are critical for control of T. cruzi infection, and CD8+ T cells recognizing the immunodominant trans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8+ T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early after T. cruzi infection of host cells, we examined the influence of IFN-I on the development of CD8+ T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20- and subdominant TSKB18-specific CD8+ T cells following T. cruzi infection. In contrast, peak TSKB20-specific CD8+ T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8+ T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8+ T-cell development.

BACKGROUND: Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. CASE PRESENTATION: A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. CONCLUSIONS: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.